Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Abstract

Myelin is critical for the proper function of the nervous system and one of the most complex cell-cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin contains a high content of lipids, and the formation of the myelin sheath requires high levels of fatty acid and lipid synthesis, together with uptake of extracellular fatty acids. Recent studies have further advanced our understanding of the metabolism and functions of myelin fatty acids and lipids. In this review, we present an overview of the basic biology of myelin lipids and recent insights on the regulation of fatty acid metabolism and functions in myelinating cells. In addition, this review may serve to provide a foundation for future research characterizing the role of fatty acids and lipids in myelin biology and metabolic disorders affecting the central and peripheral nervous system.

Keywords: Schwann cell; fatty acid; lipid; myelin; oligodendrocyte.

Figure 1

The structure of peripheral nervous system myelin sheath. Schematic representation of a (i) myelinated axon, (ii) myelin sheath, (iii) bilayer membrane, and (iv) major lipids classes. Myelin is formed by apposition of the external surfaces and internal surfaces of the myelin bilayer that constitute the intraperiodic line (IPL) and the major dense line (MDL), respectively (ii, iii). The myelin bilayer has an asymmetric lipid composition (iii, iv). Myelin protein are also asymmetrically distributed with for example PLP and P0 in the IPL and MBP and PMP2 at the MDL (iii). Cholesterol (Chl.), Galactosylceramide (Galc, cyan), Plasmalogen (PE, yellow), Phosphatidylcholine (PC, dark blue), Sphingomyelin (SM, light blue) and other phospholipids (PL, red). P0, PMP2 proteins and the enrichment of sphingomyelin in the myelin are specific to PNS myelin.

Figure 2

Simplified view of fatty acid metabolism in myelinating cells. Fatty acid (FA) uptake (FAU), synthesis (FAS), and oxidation (FAO). Tricarboxylic acid cycle (TCA). Acetyl-coA (AcCoA). Other sources include glucose and amino acids.